CYP26, a Novel Mammalian Cytochrome P450, Is Induced by Retinoic Acid and Defines a New Family

A novel member of the cytochrome P450 superfamily, CYP26, which represents a new family of cytochrome P450 enzymes, has been cloned. CYP26 mRNA is up-regulated during the retinoic acid (RA)-induced neural differentiation of mouse embryonic stem cells in vitro and is transiently expressed by embryonic stem cells undergoing predominantly non-neural differentiation. CYP26 transcript is detectable as early as embryonic day 8.5 in mouse embryos, suggesting a function for the gene in early development. CYP26 is expressed in mouse and human liver, as expected for a cytochrome P450, and is also expressed in regions of the brain and the placenta. Acute administration of 100 mg/kg all-trans-RA increases steady-state levels of transcript in the adult liver, but not in the brain. CYP26 is highly homologous to a Zebrafish gene, CYPRA1, which has been proposed to participate in the degradation of RA, but is minimally homologous to other mammalian cytochrome P450 proteins. Thus, we report the cloning of a member of a novel cytochrome P450 family that is expressed in mammalian embryos and in brain and is induced by RA in the liver.